Estimated epidemiologic parameters and morbidity associated with pandemic H1N1 influenza

Background

In the face of an influenza pandemic, accurate estimates of epidemiologic parameters are required to help guide decision-making. We sought to estimate epidemiologic parameters for pandemic H1N1 influenza using data from initial reports of laboratory-confirmed cases.

Methods

We obtained data on laboratory-confirmed cases of pandemic H1N1 influenza reported in the province of Ontario, Canada, with dates of symptom onset between Apr. 13 and June 20, 2009. Incubation periods and duration of symptoms were estimated and fit to parametric distributions. We used competing-risk models to estimate risk of hospital admission and case-fatality rates. We used a Markov Chain Monte Carlo model to simulate disease transmission.

Results

The median incubation period was 4 days and the duration of symptoms was 7 days. Recovery was faster among patients less than 18 years old than among older patients (hazard ratio 1.23, 95% confidence interval 1.06–1.44). The risk of hospital admission was 4.5% (95% CI 3.8%–5.2%) and the case-fatality rate was 0.3% (95% CI 0.1%–0.5%). The risk of hospital admission was highest among patients less than 1 year old and those 65 years or older. Adults more than 50 years old comprised 7% of cases but accounted for 7 of 10 initial deaths (odds ratio 28.6, 95% confidence interval 7.3–111.2). From the simulation models, we estimated the following values (and 95% credible intervals): a mean basic reproductive number (R₀, the number of new cases created by a single primary case in a susceptible population) of 1.31 (1.25–1.38), a mean latent period of 2.62 (2.28–3.12) days and a mean duration of infectiousness of 3.38 (2.06–4.69) days. From these values we estimated a serial interval (the average time from onset of infectiousness in a case to the onset of infectiousness in a person infected by that case) of 4–5 days.

Interpretation

The low estimates for R₀ indicate that effective mitigation strategies may reduce the final epidemic impact of pandemic H1N1 influenza.The emergence and global spread of pandemic H1N1 influenza led the World Health Organization to declare a pandemic on June 11, 2009. As the pandemic spreads, countries will need to make decisions about strategies to mitigate and control disease in the face of uncertainty.For novel infectious diseases, accurate estimates of epidemiologic parameters can help guide decision-making. A key parameter for any new disease is the basic reproductive number (R₀), defined as the average number of new cases created by a single primary case in a susceptible population. R₀ affects the growth rate of an epidemic and the final number of infected people. It also informs the optimal choice of control strategies. Other key parameters that affect use of resources, disease burden and societal costs during a pandemic are duration of illness, rate of hospital admission and case-fatality rate. Early in an epidemic, the case-fatality rate may be underestimated because of the temporal lag between onset of infection and death; the delay between initial identification of a new case and death may lead to an apparent increase in deaths several weeks into an epidemic that is an artifact of the natural history of the disease.We used data from initial reports of laboratory-confirmed pandemic H1N1 influenza to estimate epidemiologic parameters for pandemic H1N1 influenza. The parameters included R₀, incubation period and duration of illness. We also estimated risk of hospital admission and case-fatality rates, which can be used to estimate the burden of illness likely to be associated with this disease.     

Specialized Yeast Ribosomes: A Customized Tool for Selective mRNA Translation

Evidence is now accumulating that sub-populations of ribosomes - so-called specialized ribosomes - can favour the translation of subsets of mRNAs. Here we use a large collection of diploid yeast strains, each deficient in one or other copy of the set of ribosomal protein (RP) genes, to generate eukaryotic cells carrying distinct populations of altered ‘specialized’ ribosomes. We show by comparative protein synthesis assays that different heterologous mRNA reporters based on luciferase are preferentially translated by distinct populations of specialized ribosomes. These mRNAs include reporters carrying premature termination codons (PTC) thus allowing us to identify specialized ribosomes that alter the efficiency of translation termination leading to enhanced synthesis of the wild-type protein. This finding suggests that these strains can be used to identify novel therapeutic targets in the ribosome. To explore this further we examined the translation of the mRNA encoding the extracellular matrix protein laminin β3 (LAMB3) since a LAMB3-PTC mutant is implicated in the blistering skin disease Epidermolysis bullosa (EB). This screen identified specialized ribosomes with reduced levels of RP L35B as showing enhanced synthesis of full-length LAMB3 in cells expressing the LAMB3-PTC mutant. Importantly, the RP L35B sub-population of specialized ribosomes leave both translation of a reporter luciferase carrying a different PTC and bulk mRNA translation largely unaltered.     

Homology modeling, simulation and molecular docking studies of catechol-2, 3-Dioxygenase from Burkholderia cepacia: Involved in degradation of Petroleum hydrocarbons

Catechol 2, 3-dioxygenase is present in several types of bacteria and undergoes degradation of environmental pollutants through an important key biochemical pathways. Specifically, this enzyme cleaves aromatic rings of several environmental pollutants such as toluene, xylene, naphthalene and biphenyl derivatives. Hence, the importance of Catechol 2, 3-dioxygenase and its role in the degradation of environmental pollutants made us to predict the three-dimensional structure of Catechol 2, 3-dioxygenase from Burkholderia cepacia. The 10ns molecular dynamics simulation was carried out to check the stability of the modeled Catechol 2, 3- dioxygenase. The results show that the model was energetically stable, and it attains their equilibrium within 2000 ps of production MD run. The docking of various petroleum hydrocarbons into the Catechol 2,3-dioxygenase reveals that the benzene, O-xylene, Toluene, Fluorene, Naphthalene, Carbazol, Pyrene, Dibenzothiophene, Anthracene, Phenanthrene, Biphenyl makes strong hydrogen bond and Van der waals interaction with the active site residues of H150, L152, W198, H206, H220, H252, I254, T255, Y261, E271, L276 and F309. Free energy of binding and estimated inhibition constant of these compounds demonstrates that they are energetically stable in their binding cavity. Chrysene shows positive energy of binding in the active site atom of Fe. Except Pyrene all the substrates made close contact with Fe atom by the distance ranges from 1.67 to 2.43 Å. In addition to that, the above mentioned substrate except pyrene all other made π-π stacking interaction with H252 by the distance ranges from 3.40 to 3.90 Å. All these docking results reveal that, except Chrysene all other substrate has good free energy of binding to hold enough in the active site and makes strong VdW interaction with Catechol-2,3-dioxygenase. These results suggest that, the enzyme is capable of catalyzing the above-mentioned substrate.     

Isolation and characterisation of a bovine cDNA encoding eukaryotic initiation factor 2 alpha

Two cDNA clones have been isolated, from a bovine lymphosarcoma library, that encode the alpha-subunit of eukaryotic initiation factor 2 (eIF-2 alpha). The predicted 315 amino acid sequence showed more than 99% amino acid identity with rat and human eIF-2 alpha. Galactose-regulated expression of a full length bovine eIF-2 alpha cDNA in yeast resulted in the synthesis of a polypeptide of the predicted molecular mass (36 kDa). Furthermore, the expressed polypeptide cross-reacted with an antibody raised against rabbit eIF-2 alpha confirming the identity of the cDNA.     

Social complexity in bees is not sufficient to explain lack of reversions to solitary living over long time scales

Background  

The major lineages of eusocial insects, the ants, termites, stingless bees, honeybees and vespid wasps, all have ancient origins (≥ 65 mya) with no reversions to solitary behaviour. This has prompted the notion of a 'point of no return' whereby the evolutionary elaboration and integration of behavioural, genetic and morphological traits over a very long period of time leads to a situation where reversion to solitary living is no longer an evolutionary option.     

Efficient translation of synthetic and natural mRNAs in an mRNA-dependent cell-free system from the dimorphic fungus Candida albicans.

An mRNA-dependent cell-free translation system has been developed from the human pathogenic fungus Candida albicans using either S30 or S100 lysates prepared from glass-bead-disrupted whole cells. Translation of the synthetic template poly(U) in this system is highly efficient at temperatures up to 37 degrees C and is ATP-dependent. Studies using a range of elongation-specific inhibitors suggest that the mechanism of translational elongation in C. albicans is similar to that of another yeast, Saccharomyces cerevisiae. A micrococcal-nuclease-treated C. albicans S100 lysate was able to translate exogenously-supplied homologous mRNAs, and a range of heterologous natural mRNAs, using an initiation mechanism that is inhibited by the antibiotic edeine and the 5' cap analogue 7-methylguanosine 5'-monophosphate (m7GMP). As with cell-free lysates prepared from S. cerevisiae, the C. albicans lysate is unable to initiate translation upon natural mRNAs at temperatures above 20 degrees C.     

Translation elongation factor 3: a fungus-specific translation factor?

Fungi appear to be unique in their requirement for a third soluble translation elongation factor. This factor, designated elongation factor 3 (EF-3), was first described in the yeast Saccharomycescerevisiae and has subsequently been identified in a wide range of fungal species Including Candida albicans and Schizo-saccharomyces pombe. EF-3 exhibits ribosome-dependent ATPase and GTPase activities that are not intrinsic to the fungal ribosome, but which are essential for translation elongation. Recent studies on the structure of EF-3 from several fungal species have shown that it consists of a repeated domain, with each domain containing the expected putative ATP- and GTP-binding motifs. Overall, EF-3 shows striking amino acid similarity to members of the ATP-binding Cassette (ABC) family of membrane-associated transport proteins although EF-3 is not itself directly membrane-associated. Regions of the EF-3 polypeptide also show structural homology with other translation-associated factors including aminoacyl-tRNA synthetases and the Escherichia coli ribosomal protein S5. While the precise role of EF-3 in the translation elongation cycle remains to be defined, recent evidence suggests that it may be involved in optimizing accuracy during mRNA decoding at the ribosomal A site. Furthermore, the essential nature of EF-3 with respect to the fungal cell indicates that it may be an effective antifungal target. Its apparently ubiquitous occurrence throughout the fungal kingdom also suggests that it may be a useful fungal taxonomic marker.